Endothelial differentiation gene (EDG) receptors are a new family of eight G protein-coupled receptors for the lysophospholipids lysophosphatitic acid and sphingosine-1-phosphate. The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction (Pyne and Pyne, (2000) Biochem J 349: 385-402; MacLennan et al., (2001), J. of Neurosci. 14: 203-209). Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal through a set of G protein-coupled receptors known as EDG receptors. EDG5 (endothelial differentiation gene 5; also termed AGR16/H218) is a functional receptor for S1P. The size of the EDG5 protein is 353 amino acids and the EDG5 gene is located on chromosome 19p13.2.
Mammalian EDG-5 Receptor homologs are described in WO 99/33972.
Developmental studies in Zebrafish have indicated that S1P signaling via the EDG5 like receptor Miles Apart is essential for heart development. The presumed function of the EDG5 homologue in Zebrafish development and its expression in the heart suggests that it may play a critical role in the development and/or function of the cardiovascular system (Kupperman et al., (2000), Nature 406: 192-195).
In order to analyze potential effects of EDG5 polymorphisms in humans, the V286A polymorphism (amino acid exchange valine to alanine at position 286 of the EDG5 protein) of the EDG5 protein was studied in a clinical patient cohort enriched for cardiovascular outcomes. So far, no data was available about the clinical effects of EDG5 variants in humans. (NCBI accession number for EDG5 protein sequence:
NP—004221 and NCBI accession number for EDG5 nucleotide sequence: AF034780).
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